The platelet antigen system, Pl.sup.A, is associated with two clinical syndromes, neonatal alloimmune thrombocytopenia (NAIT) and posttranfusion purpura (PTP) Aster, The immunologic thrombocytopenias, Kunicki and George, eds., Platelet Immunobiology, 387, Philadelphia, Pa. (1989)!. NAIT is a bleeding disorder of newborns with increased platelet destruction caused by tranplacentally transfered maternal platelet specific antibodies and is estimated to occur at a frequency of 1/1,000 births Blanchette et al., Curr. Stud. Hematol. Blood Tranf., 52:87 (1986)!. PTP is an antibody-mediated thrombocytopenia in response to platelet incompatibility following a blood tranfusion. The most common cause of both NAIT and PTP in the Caucasian population is the Pl.sup.A1 alloantigen.
The alloantigenic determinant responsible for eliciting anti-Pl.sup.A1 antibodies is present on the platelet membrane GPIIIa Kunicki et al, Mol. Immunol., 16:353 (1979)!. The Pl.sup.A1 and Pl.sup.A2 phenotypes are dependent on the presence of a thymidine (T) or cytidine (C), respectively, at base 196 of the GPIIIa cDNA sequence Newman et al, J. Clin. Inves., 83:1778 (1989)!.
The T.fwdarw.C base change results in a leucine/proline polymorphism at residue 33 of mature GPIIIa. Although the leucine to proline polymorphism at the amino terminal end of GPIIIa is responsible for the Pl.sup.A1 /Pl.sup.A2 platelet allotypes Goldberg et al., Blood, 78:681 (1989)!, synthetic linear peptides containing this polymorphism Flug et al, Blood, 77:1964 (1991)! did not react with anti-Pl.sup.A1 antibodies, suggesting that the leucine.sup.33 /proline.sup.33 polymorphism might affect global folding or post-translational processing to assemble the Pl.sup.A1 epitope.